1. Field of the Invention
The present invention relates to a novel human myelomonocyte interferon-gamma, a process for preparing this interferon-gamma, and its use.
More particularly, the present invention relates to a novel human myelomonocyte interferon-gamma, and a process for preparing this interferon-gamma, characterized by allowing an established human myelomonocyte capable of producing myelomonocyte interferon-gamma to produce the interferon-gamma, and recovering the accumulation; a process for preparing a monoclonal anti-interferon-gamma antibody using the myelomonocyte; and a method for purifying the interferon-gamma using the monoclonal antibody, as well as to a prophylactic and therapeutic agent for interferon-gamma susceptible disease, these agents containing the human myelomonocyte interferon-gamma as an effective ingredient thereof.
2. Description of the Prior Art
As described in Sigeyasy Kobayashi, "Interferon", published by Kodansha Co., Ltd. Tokyo, Japan (1975), D. A. J. Tyrrell, "Interferon and its Clinical Potential", published by William Heinemann Medical Books Ltd., London (1976), and Protein, Nucleic Acid and Enzyme, Vol. 21, No. 4, pp. 245-333 (1976), interferon is a name used to designate glycoproteins that can be extracellularly induced in a viable cell by subjecting the cell to the action of an interferon inducer, such as a virus, a bacterium, a protozoon, rickettsia, nucleic acid endotoxin, or polysaccharide. These glycoproteins also are capable of nonspecifically inhibiting viral growth.
This activity has made interferons potential prophylactic and therapeutic agents for viral diseases. Recent studies revealed that interferons exert an antioncotic activity on viral tumors, as well as on nonviral tumors. Because of the activity of interferons, there is much interest in developing pharmaceuticals using interferons.
Interferons include interferon-alpha (or leukocyte interferon), interferon-beta (or fibroblast interferon), and interferon-gamma (or immune interferon). Preparation of interferon-alpha and interferon-beta has been effected by using leukocytes and fibroblast cells. Recently, pharmaceuticals containing these interferons have been commercialized.
The interferons hereinafter will be abbreviated as "IFN-alpha", IFN-beta", and "IFN-gamma", occasionally with the prefix "Hu" indicating human origin.
Although various methods have been proposed for preparing HuIFN-gamma, no method has as yet been practiced on an industrial scale.
The methods using leukocytes or T lymphocytes derived from human peripheral blood, as disclosed, for example, in Japanese Patent Laid-Open Publications Nos. 58,891/82, 82,092/94, 70,099/85, 87,300/85, 129,700/85 and 149,600/85, International Patent Publication in Japanese Nos. 500,961/82 and 502,032/83, are not commercially useful because it is difficult to obtain an ample supply of the starting cells and these cells do not produce sufficient HuIFN to be commercially useful.
Japanese Patent Laid-Open No. 98,118/80 discloses a method wherein a human cell, which is obtained by implanting an established human cell into a non-human warm-blooded animal, or placing the cell into a diffusion chamber provided inside or outside of the body of a non-human warm-blooded animal, and allowing the cell to proliferate while allowing the cell to receive the nutrient body fluid from the animal, is used for preparing HuIFN-gamma. This method is characterized by an ample supply of the cell which is the starting material.
We found that the HuIFN-gamma productivity of the method varies with the type of the human cell used. Thus, the method can be improved to prepare consistently high-titered HuIFN-gamma so as to be practical for use on an industrial scale.
It is known that HuIFN-gamma is much stronger in cytostatic and antioncotic activities as compared with HuIFN-alpha or HuIFN-beta. Also, it is known that the combination of HuIFN-gamma with HuIFN-alpha and/or HuIFN-beta augments the antiviral, cytostatic and antioncotic activities of HuIFN-gamma. For these reasons, development of an industrial-scale preparation of HuIFN-gamma has been in great demand.